Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Two chemosensory receptors together mediate carbon dioxide detection in Drosophila

Abstract

Blood-feeding insects, including the malaria mosquito Anopheles gambiae, use highly specialized and sensitive olfactory systems to locate their hosts. This is accomplished by detecting and following plumes of volatile host emissions, which include carbon dioxide (CO2)1. CO2 is sensed by a population of olfactory sensory neurons in the maxillary palps of mosquitoes2,3 and in the antennae of the more genetically tractable fruitfly, Drosophila melanogaster4. The molecular identity of the chemosensory CO2 receptor, however, remains unknown. Here we report that CO2-responsive neurons in Drosophila co-express a pair of chemosensory receptors, Gr21a and Gr63a, at both larval and adult life stages. We identify mosquito homologues of Gr21a and Gr63a, GPRGR22 and GPRGR24, and show that these are co-expressed in A. gambiae maxillary palps. We show that Gr21a and Gr63a together are sufficient for olfactory CO2-chemosensation in Drosophila. Ectopic expression of Gr21a and Gr63a together confers CO2 sensitivity on CO2-insensitive olfactory neurons, but neither gustatory receptor alone has this function. Mutant flies lacking Gr63a lose both electrophysiological and behavioural responses to CO2. Knowledge of the molecular identity of the insect olfactory CO2 receptors may spur the development of novel mosquito control strategies designed to take advantage of this unique and critical olfactory pathway. This in turn could bolster the worldwide fight against malaria and other insect-borne diseases.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Gr21a and Gr63a are co-expressed in the CO 2 -responsive chemosensory neurons.
Figure 2: Expression of both Gr21a and Gr63a confers CO 2 sensitivity on normally CO 2 -insensitive neurons.
Figure 3: Gr63a1 mutants are electrophysiologically and behaviourally insensitive to CO2.
Figure 4: Gr63a 1 mutants and the GAL4 and UAS controls are all indifferent to CO 2 in a T-maze, whereas wild-type and heterozygous Gr63a 1 flies show robust avoidance.

References

  1. Gillies, M. T. The role of carbon dioxide in host-finding in mosquitoes (Diptera:Culicidae): a review. Bull. Entomol. Res. 70, 525–532 (1980)

    Article  Google Scholar 

  2. Kellogg, F. E. Water vapour and carbon dioxide receptors in Aedes aegypti. J. Insect Physiol. 16, 99–108 (1970)

    Article  CAS  Google Scholar 

  3. Grant, A. J., Wigton, B. E., Aghajanian, J. G. & O’Connell, R. J. Electrophysiological responses of receptor neurons in mosquito maxillary palp sensilla to carbon dioxide. J. Comp. Physiol. A 177, 389–396 (1995)

    Article  CAS  Google Scholar 

  4. de Bruyne, M., Foster, K. & Carlson, J. R. Odor coding in the Drosophila antenna. Neuron 30, 537–552 (2001)

    Article  CAS  Google Scholar 

  5. Nicolas, G. & Sillans, D. Immediate and latent effects of carbon dioxide on insects. Annu. Rev. Entomol. 34, 97–116 (1989)

    Article  CAS  Google Scholar 

  6. Thom, C., Guerenstein, P. G., Mechaber, W. L. & Hildebrand, J. G. Floral CO2 reveals flower profitability to moths. J. Chem. Ecol. 30, 1285–1288 (2004)

    Article  CAS  Google Scholar 

  7. Southwick, E. E. & Moritz, R. F. A. Social control of air ventilation in colonies of honey bees, Apis mellifera. J. Insect Physiol. 33, 623–626 (1987)

    Article  Google Scholar 

  8. Takken, W. & Knols, B. G. Odor-mediated behavior of Afrotropical malaria mosquitoes. Annu. Rev. Entomol. 44, 131–157 (1999)

    Article  CAS  Google Scholar 

  9. Suh, G. S. et al. A single population of olfactory sensory neurons mediates an innate avoidance behaviour in Drosophila. Nature 431, 854–859 (2004)

    Article  ADS  CAS  Google Scholar 

  10. Faucher, C., Forstreuter, M., Hilker, M. & de Bruyne, M. Behavioral responses of Drosophila to biogenic levels of carbon dioxide depend on life-stage, sex and olfactory context. J. Exp. Biol. 209, 2739–2748 (2006)

    Article  CAS  Google Scholar 

  11. Stange, G. & Stowe, S. Carbon-dioxide sensing structures in terrestrial arthropods. Microsc. Res. Tech 47, 416–427 (1999)

    Article  CAS  Google Scholar 

  12. Scott, K. et al. A chemosensory gene family encoding candidate gustatory and olfactory receptors in Drosophila. Cell 104, 661–673 (2001)

    Article  CAS  Google Scholar 

  13. Robertson, H. M., Warr, C. G. & Carlson, J. R. Molecular evolution of the insect chemoreceptor gene superfamily in Drosophila melanogaster. Proc. Natl Acad. Sci. USA 100, (Suppl. 2)14537–14542 (2003)

    Article  ADS  CAS  Google Scholar 

  14. Wang, Z., Singhvi, A., Kong, P. & Scott, K. Taste representations in the Drosophila brain. Cell 117, 981–991 (2004)

    Article  CAS  Google Scholar 

  15. Fishilevich, E. & Vosshall, L. B. Genetic and functional subdivision of the Drosophila antennal lobe. Curr. Biol. 15, 1548–1553 (2005)

    Article  CAS  Google Scholar 

  16. Hill, C. A. et al. G protein-coupled receptors in Anopheles gambiae. Science 298, 176–178 (2002)

    Article  ADS  CAS  Google Scholar 

  17. Dobritsa, A. A. van der Goes van Naters, W. Warr, C. G., Steinbrecht, R. A. & Carlson, J. R. Integrating the molecular and cellular basis of odor coding in the Drosophila antenna. Neuron 37, 827–841 (2003)

    Article  CAS  Google Scholar 

  18. Benton, R., Sachse, S., Michnick, S. W. & Vosshall, L. B. Atypical membrane topology and heteromeric function of Drosophila odorant receptors in vivo. PLoS Biol. 4, e20 (2006)

    Article  Google Scholar 

  19. Hallem, E. A. & Carlson, J. R. Coding of odors by a receptor repertoire. Cell 125, 143–160 (2006)

    Article  CAS  Google Scholar 

  20. Shanbhag, S. R., Mueller, B. & Steinbrecht, R. A. Atlas of olfactory organs of Drosophila melanogaster. 1. Types, external organization, innervation and distribution of olfactory sensilla. Int. J. Insect Morphol. Embryol. 28, 377–397 (1999)

    Article  Google Scholar 

  21. Gong, W. J. & Golic, K. G. Ends-out, or replacement, gene targeting in Drosophila. Proc. Natl Acad. Sci. USA 100, 2556–2561 (2003)

    Article  ADS  CAS  Google Scholar 

  22. Larsson, M. C. et al. Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron 43, 703–714 (2004)

    Article  CAS  Google Scholar 

  23. Gray, J. M. et al. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 430, 317–322 (2004)

    Article  ADS  CAS  Google Scholar 

  24. Wingrove, J. A. & O’Farrell, P. H. Nitric oxide contributes to behavioral, cellular, and developmental responses to low oxygen in Drosophila. Cell 98, 105–114 (1999)

    Article  CAS  Google Scholar 

  25. Verma, A., Hirsch, D. J., Glatt, C. E., Ronnett, G. V. & Snyder, S. H. Carbon monoxide: a putative neural messenger. Science 259, 381–384 (1993)

    Article  ADS  CAS  Google Scholar 

  26. Reinking, J. et al. The Drosophila nuclear receptor e75 contains heme and is gas responsive. Cell 122, 195–207 (2005)

    Article  CAS  Google Scholar 

  27. Hou, S. et al. Myoglobin-like aerotaxis transducers in Archaea and Bacteria. Nature 403, 540–544 (2000)

    Article  ADS  CAS  Google Scholar 

  28. Laissue, P. P. et al. Three-dimensional reconstruction of the antennal lobe in Drosophila melanogaster. J. Comp. Neurol. 405, 543–552 (1999)

    Article  CAS  Google Scholar 

  29. Fishilevich, E. et al. Chemotaxis behavior mediated by single larval olfactory neurons in Drosophila. Curr. Biol. 15, 2086–2096 (2005)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank P. Howell and M. Q. Benedict of the CDC and MR4 for providing us with mosquitoes contributed by W. E. Collins; K. Kay and K. Fishilevich for technical assistance; and R. Axel, C. Bargmann, K. J. Lee and members of the Vosshall Laboratory for comments on the manuscript. This work was funded in part by a grant to R. Axel and L.B.V. from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative and by an NIH grant to L.B.V. Support was contributed to W.D.J. from an NIH MSTP grant, to P.C. from the Jane Coffin Childs Memorial Fund for Medical Research and to I.G.K. from the Human Frontier Science Program.

Author Contributions W.D.J. carried out all the experiments and analysed the data. P.C. and I.G.K. generated and characterized the Gr63a-sytRFP transgene in the laboratory of S. L. Zipursky at UCLA. W.D.J. and L.B.V. together designed the experiments, interpreted the results, produced the figures, and wrote the paper.

Genbank accession numbers for A. gambiae genes in this paper are: GPROR7 (AY843205), GPRGR22 (DQ989011) and GPRGR24 (DQ989013). Genbank accession numbers for D. melanogaster genes in this paper are: Gr10a (DQ989010), Gr21a (DQ989014) and Gr63a (DQ989012).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leslie B. Vosshall.

Ethics declarations

Competing interests

Genbank accession numbers for A. gambiae genes in this paper are: GPROR7 (AY843205), GPRGR22 (DQ989011) and GPRGR24 (DQ989013). Genbank accession numbers for D. melanogaster genes in this paper are: Gr10a (DQ989010), Gr21a (DQ989014) and Gr63a (DQ989012). Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains detailed Supplementary Methods. (PDF 112 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jones, W., Cayirlioglu, P., Grunwald Kadow, I. et al. Two chemosensory receptors together mediate carbon dioxide detection in Drosophila. Nature 445, 86–90 (2007). https://doi.org/10.1038/nature05466

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05466

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing